Journal
JOURNAL OF PROTEOME RESEARCH
Volume 10, Issue 8, Pages 3712-3719Publisher
AMER CHEMICAL SOC
DOI: 10.1021/pr200339n
Keywords
sodium channel; post-translational modification; arginine methylation; channelopathy; sudden cardiac death; arrhythmia; Brugada syndrome; long QT syndrome
Categories
Funding
- Fundacio Obra Social La Caixa (Spain)
- Fundacion Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC, Spain)
- Instituto de Salud Carlos III (ISCIII)
Ask authors/readers for more resources
The alpha subunit of the cardiac sodium channel (Na(v)1.5) is an essential protein in the initial depolarization phase of the cardiomyocyte action potential. Post-translational modifications such as phosphorylation are known to regulate Na(v)1.5 function. Here, we used a proteomic approach for the study of the post-translational modifications of Na(v)1.5 using tsA201 cells as a model system. We generated a stable cell line expressing Na(v)1.5, purified the sodium channel, and analyzed Na(v)1.5 by MALDI-TOF and LC-MS/MS. We report the identification of arginine methylation as a novel post-translational modification of Na(v)1.5. R513, R526, and R680, located in the linker between domains I and H in Na(v)1.5, were found in mono- or dimethylated states. The functional relevance of arginine methylation in Na(v)1.5 is underscored by the fact that R526H and R680H are known Na(v)1.5 mutations causing Brugada and long QT type 3 syndromes, respectively. Our work describes for the first time arginine methylation in the voltage-gated ion channel superfamily.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available